Neural Circuits: Reduced Inhibition in Fragile X Syndrome

Golovin, Randall M.; Broadie, Kendal

doi:10.1016/j.cub.2017.03.011

Cited by 8 publications

(3 citation statements)

References 21 publications

(24 reference statements)

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“…The loss of critical period remodeling in OSNs lacking the Or42a EB odorant receptor indicates that the mechanism requires olfactory reception in the specific OSN, and lateral communication between different OSN classes within the AL is not sufficient to cause remodeling (Acebes et al, 2011(Acebes et al, , 2012Franco et al, 2017;Golovin and Broadie, 2017). The maintenance of OSN critical period remodeling with tetanus toxin blockade does not exclude electrical synapse involvement, which ise not affected by the neurotoxin (Sweeney et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

“…This is a very important consideration because AL lateral connections from other activated olfactory sensory neurons could possibly affect VM7 critical period development. Indeed, recent work has demonstrated that altered lateral inhibition in the AL can modulate olfactory sensory processing and change olfactory behavioral outputs (Acebes et al, 2011(Acebes et al, , 2012Franco et al, 2017;Golovin and Broadie, 2017). We therefore tested whether the specific activation of Or42a receptors is required for critical period synaptic remodeling of Or42a OSNs within the VM7 glomerulus.…”

Section: Or42a Olfactory Reception Is Required For Critical Period Rementioning

confidence: 94%

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Activity-Dependent Remodeling ofDrosophilaOlfactory Sensory Neuron Brain Innervation during an Early-Life Critical Period

Golovin

Vest²,

Vita³

et al. 2019

J. Neurosci.

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Critical periods are windows of development when the environment has a pronounced effect on brain circuitry. Models of neurodevelopmental disorders, including autism spectrum disorders, intellectual disabilities, and schizophrenia, are linked to disruption of critical period remodeling. Critical periods open with the onset of sensory experience; however, it remains unclear exactly how sensory input modifies brain circuits. Here, we examine olfactory sensory neuron (OSN) innervation of the Drosophila antennal lobe of both sexes as a genetic model of this question. We find that olfactory sensory experience during an early-use critical period drives loss of OSN innervation of antennal lobe glomeruli and subsequent axon retraction in a dose-dependent mechanism. This remodeling does not result from olfactory receptor loss or OSN degeneration, but rather from rapid synapse elimination and axon pruning in the target olfactory glomerulus. Removal of the odorant stimulus only during the critical period leads to OSN reinnervation, demonstrating that remodeling is transiently reversible. We find that this synaptic refinement requires the OSN-specific olfactory receptor and downstream activity. Conversely, blocking OSN synaptic output elevates glomeruli remodeling. We find that GABAergic neurotransmission has no detectable role, but that glutamatergic signaling via NMDA receptors is required for OSN synaptic refinement. Together, these results demonstrate that OSN inputs into the brain manifest robust, experience-dependent remodeling during an early-life critical period, which requires olfactory reception, OSN activity, and NMDA receptor signaling. This work reveals a pathway linking initial olfactory sensory experience to glutamatergic neurotransmission in the activity-dependent remodeling of brain neural circuitry in an early-use critical period.

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Section: Discussionmentioning

confidence: 99%

Section: Or42a Olfactory Reception Is Required For Critical Period Rementioning

confidence: 94%

Activity-Dependent Remodeling ofDrosophilaOlfactory Sensory Neuron Brain Innervation during an Early-Life Critical Period

Golovin

Vest²,

Vita³

et al. 2019

J. Neurosci.

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“…In animal models of TCD, hyperpolarization of thalamic relay neurons has been observed to lead to alterations in firing patterns of low-threshold calcium spikes which are reflected in local field potentials as elevated theta rhythmicity(Jeanmonod et al, 1993; Jeanmonod et al, 2003; Llinás et al, 1999). A dominant theta rhythm may be reflective of a diminished inhibitory capacity at a systems-level resulting in excess asynchronous gamma activity and the so-called gamma “edge effect” (Golovin & Broadie, 2017; Llinás et al, 1999; Paluszkiewicz et al, 2011; R et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Empirical Frequency Bound Derivation Reveals Prominent Mid-Frontal Alpha Associated with Neurosensory Dysfunction in Fragile X Syndrome

Pedapati

Sweeney

Schmitt

et al. 2022

Preprint

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The FMR1 gene is inactive in Fragile X syndrome (FXS), resulting in low levels of FMRP and consequent neurochemical, synaptic and local circuit neurophysiological alterations in the fmr1 KO mouse. In FXS patients, electrophysiological studies of have demonstrated a marked reduction in global alpha activity and regional increases in gamma oscillations that have been associated with intellectual disability and sensory hypersensitivity. Since alpha activity is associated with thalamocortical function that has widely distributed modulatory effects on neocortical excitability, insight into alpha physiology may provide insight into systems-level disease mechanisms. Herein, we took a data driven approach to clarify the temporal and spatial properties of alpha and theta activity in participants with FXS. High-resolution resting-state EEG data was collected from participants affected by FXS (n=65) and matched controls (n=70). We used a multivariate technique to empirically classify neural oscillatory bands based on their coherent spatiotemporal patterns. Participants with FXS demonstrated: 1) a redistribution of lower-frequency boundaries indicating a "slower" dominant alpha rhythm, 2) an anteriorization of alpha frequency activity, and 3) a correlation of increased individualized alpha power measurements with auditory neurosensory dysfunction. These findings suggest an important role for alterations in thalamocortical physiology for the well-established neocortical hyper-excitability in FXS, and thus a role for neural systems level disruption to cortical hyperexcitability that has been studied primarily at the local circuit level in mouse model research.

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Postreproductive killer whale grandmothers improve the survival of their grandoffspring

Nattrass

Croft

Ellis

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Understanding why females of some mammalian species cease ovulation prior to the end of life is a long-standing interdisciplinary and evolutionary challenge. In humans and some species of toothed whales, females can live for decades after stopping reproduction. This unusual life history trait is thought to have evolved, in part, due to the inclusive fitness benefits that postreproductive females gain by helping kin. In humans, grandmothers gain inclusive fitness benefits by increasing their number of surviving grandoffspring, referred to as the grandmother effect. Among toothed whales, the grandmother effect has not been rigorously tested. Here, we test for the grandmother effect in killer whales, by quantifying grandoffspring survival with living or recently deceased reproductive and postreproductive grandmothers, and show that postreproductive grandmothers provide significant survival benefits to their grandoffspring above that provided by reproductive grandmothers. This provides evidence of the grandmother effect in a nonhuman menopausal species. By stopping reproduction, grandmothers avoid reproductive conflict with their daughters, and offer increased benefits to their grandoffspring. The benefits postreproductive grandmothers provide to their grandoffspring are shown to be most important in difficult times where the salmon abundance is low to moderate. The postreproductive grandmother effect we report, together with the known costs of late-life reproduction in killer whales, can help explain the long postreproductive life spans of resident killer whales.

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Neural Circuits: Reduced Inhibition in Fragile X Syndrome

Cited by 8 publications

References 21 publications

Activity-Dependent Remodeling ofDrosophilaOlfactory Sensory Neuron Brain Innervation during an Early-Life Critical Period

Activity-Dependent Remodeling ofDrosophilaOlfactory Sensory Neuron Brain Innervation during an Early-Life Critical Period

Empirical Frequency Bound Derivation Reveals Prominent Mid-Frontal Alpha Associated with Neurosensory Dysfunction in Fragile X Syndrome

Postreproductive killer whale grandmothers improve the survival of their grandoffspring

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